7CZD

Crystal structure of PD-L1 in complex with a VHH

Summary for 7CZD

• Entry DOI: 10.2210/pdb7czd/pdb
• Descriptor: anti-PD-L1 VHH, Programmed cell death 1 ligand 1, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: antibody, complex, vhh, immune system
• Biological source: Lama glama; More
• Total number of polymer chains: 4
• Total formula weight: 52703.35

Authors

Wang, C. (deposition date: 2020-09-08, release date: 2021-07-14, Last modification date: 2023-11-29)

Primary citation

Zhai, T.,Wang, C.,Xu, Y.,Huang, W.,Yuan, Z.,Wang, T.,Dai, S.,Peng, S.,Pang, T.,Jiang, W.,Huang, Y.,Zou, Y.,Xu, Y.,Sun, J.,Gong, X.,Zhang, J.,Tsun, A.,Li, B.,Miao, X.
Generation of a safe and efficacious llama single-domain antibody fragment (vHH) targeting the membrane-proximal region of 4-1BB for engineering therapeutic bispecific antibodies for cancer.
J Immunother Cancer, 9:-, 2021

PubMed Abstract: The discovery of checkpoint inhibitors towards cytotoxic T-lymphocyte protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) has been revolutionary for the treatment of cancers. These therapies have only offered an average of 20%-30% response rates across the tumor spectrum and the combination of agonists towards the tumor-necrosis superfamily members, such as 4-1BB and CD40, has shown potent efficacy in preclinical studies; however, these agonists have exhibited high degrees of toxicity with limited efficacy in human trials. In this study, we have generated a single-domain antibody towards a unique epitope of 4-1BB that limits its potential on-target toxicity while maintaining sufficient potency. This 4-1BB binder is ideal for use in the engineering of multispecific antibodies to localize 4-1BB activation within the tumor microenvironment, as shown here by a anti-PD-L1/4-1BB bispecific candidate (PM1003).

PubMed: 34172514
DOI: 10.1136/jitc-2020-002131

Experimental method

X-RAY DIFFRACTION (1.64 Å)